Important risk factors for breast cancer are age, gender, reproductive history, hormonal factors, and family history. Although a family history of breast and/or ovarian cancer is common in patients diagnosed with breast cancer, less than ten percent of all breast cancers are associated with genetic mutations.

Assay of hormone receptors (estrogen [ER] and progesterone [PR] receptors) is an important component of the pathologic evaluation of breast cancer, for both prognostic and predictive purposes, as patients with hormone receptor-positive tumors benefit from the addition of endocrine treatments.

What are the Molecular SubTypes of Breast Cancer:

Molecular profiling, based upon variations in gene expression, has identified several distinct breast cancer subtypes, named the breast cancer intrinsic subtypes.

Luminal A and B are the most common subtypes and make up the majority of estrogen receptor (ER)-positive breast cancers. Luminal A tumors carry the best prognosis of all of the subtypes. Luminal B tumors have a lower expression of ER-related genes, variable expression of the human epidermal growth factor receptor-2 (HER2) cluster, and higher expression of the proliferation cluster. Consequently, luminal B tumors have a poorer prognosis.

HER2-enriched (HER2+/ER-) subtype cancers are typically negative for ER and progesterone receptor (PR), and positive for HER2. The poor prognosis associated with these tumors has been undoubtedly altered by HER2-directed therapies

Basal-like tumors are typically ER-negative, PR-negative, and HER2-negative on clinical assays, which has prompted the nickname "triple-negative" to describe them. They have a strong association with cancers arising in breast cancer gene 1, early onset (BRCA1) mutation carriers and are overrepresented in breast cancer developing during the premenopausal years and in African-American women. They have the worst prognosis of the subtypes

Staging of Breast Cancer:

Tumor node metastases (TNM) staging system for carcinoma of the breast

Primary tumor (T)

TX

Primary tumor cannot be assessed

T0

No evidence of primary tumor

Tis

Carcinoma in situ

Tis (DCIS)

Ductal carcinoma in situ

Tis (LCIS)

Lobular carcinoma in situ

Tis (Paget's)

Paget's disease (Paget disease) of the nipple NOT associated with invasive carcinoma and/or carcinoma in situ (DCIS and/or LCIS) in the underlying breast parenchyma. Carcinomas in the breast parenchyma associated with Paget's disease are categorized based on the size and characteristics of the parenchymal disease, although the presence of Paget's disease should still be noted.

T1

Tumor ≤20 mm in greatest dimension

T1mi

Tumor ≤1 mm in greatest dimension

T1a

Tumor >1 mm but ≤5 mm in greatest dimension

T1b

Tumor >5 mm but ≤10 mm in greatest dimension

T1c

Tumor >10 mm but ≤20 mm in greatest dimension

T2

Tumor >20 mm but ≤50 mm in greatest dimension

T3

Tumor >50 mm in greatest dimension

T4◊

Tumor of any size with direct extension to the chest wall and/or to the skin (ulceration or skin nodules)

T4a

Extension to the chest wall, not including only pectoralis muscle adherence/invasion

T4b

Ulceration and/or ipsilateral satellite nodules and/or edema (including peau d'orange) of the skin, which do not meet the criteria for inflammatory carcinoma

T4c

Both T4a and T4b

T4d

Inflammatory carcinoma§

The use of neoadjuvant therapy does not change the clinical (pretreatment) stage. Clinical (pretreatment) T will be defined by clinical and radiographic findings, while y pathologic (posttreatment) T will be determined by pathologic size and extension. The ypT will be measured as the largest single focus of invasive tumor, with the modifier "m" indicating multiple foci. The measurement of the largest tumor focus should not include areas of fibrosis within the tumor bed.

Metastases in ten or more axillary lymph nodes; or in infraclavicular (level III axillary) lymph nodes; or in clinically detected◊◊ ipsilateral internal mammary lymph nodes in thepresenceof one or more positive level I, II axillary lymph nodes; or in more than three axillary lymph nodes and in internal mammary lymph nodes with micrometastases or macrometastases detected by sentinel lymph node biopsy but not clinically detected ΔΔ; or in ipsilateral supraclavicular lymph nodes

Metastases in clinically detected◊◊ ipsilateral internal mammary lymph nodes in thepresenceof one or more positive axillary lymph nodes; or in more than three axillary lymph nodes and in internal mammary lymph nodes with micrometastases or macrometastases detected by sentinel lymph node biopsy but not clinically detected ΔΔ

pN3c

Metastases in ipsilateral supraclavicular lymph nodes

Posttreatment ypN

- Post-treatment yp "N" should be evaluated as for clinical (pretreatment) "N" methods above. The modifier "sn" is used only if a sentinel node evaluation was performed after treatment. If no subscript is attached, it is assumed that the axillary nodal evaluation was by axillary node dissection (AND).

- The X classification will be used (ypNX) if no yp posttreatment SN or AND was performed

- N categories are the same as those for pN

Distant metastasis (M)

M0

No clinical or radiographic evidence of distant metastases

cM0(i+)

No clinical or radiographic evidence of distant metastases, but deposits of molecularly or microscopically detected tumor cells in circulating blood, bone marrow, or other nonregional nodal tissue that are no larger than 0.2 mm in a patient without symptoms or signs of metastases

Posttreatment yp M classification.The M category for patients treated with neoadjuvant therapy is the category assigned in the clinical stage, prior to initiation of neoadjuvant therapy. Identification of distant metastases after the start of therapy in cases where pretherapy evaluation showed no metastases is considered progression of disease. If a patient was designated to have detectable distant metastases (M1) before chemotherapy, the patient will be designated as M1 throughout.

Anatomic stage/prognostic groups§§

0

Tis

N0

M0

IA

T1 ¥¥

N0

M0

IB

T0

N1mi

M0

T1 ¥¥

N1mi

M0

IIA

T0

N1 ‡‡

M0

T1 ¥¥

N1 ‡‡

M0

T2

N0

M0

IIB

T2

N1

M0

T3

N0

M0

IIIA

T0

N2

M0

T1 ¥¥

N2

M0

T2

N2

M0

T3

N1

M0

T3

N2

M0

IIIB

T4

N0

M0

T4

N1

M0

T4

N2

M0

IIIC

Any T

N3

M0

IV

Any T

Any N

M1

.

Treatment of hormone receptor positive breast cancer:

The treatment of early stage breast cancer includes the treatment of locoregional disease with surgery, radiation therapy, or both, and the treatment of systemic disease with one or a combination of chemotherapy, endocrine therapy, or biologic therapy.

Neoadjuvant (before Surgery) systemic therapy has become a frequently used option in the treatment of breast cancer.

For patients with locally advanced, inoperable breast cancer and inflammatory breast cancer, neoadjuvant systemic therapy is standard treatment. The goal of neoadjuvant systemic therapy is to induce tumor response, to facilitate local control through surgical resection and radiation therapy, and to improve disease-free and overall survival.

For patients with early stage, operable breast cancer, neoadjuvant systemic therapy may be used rather than primary surgery in order to increase the chance of successful breast conserving surgery. For these patients, neoadjuvant systemic therapy results in long-term distant disease-free survival and overall survival comparable to that achieved with adjuvant systemic therapy.

Specialties

Hematology/Oncology - Internal Medicine

Internal Medicine

Roles

Interim Deputy Director, Sylvester Comprehensive Cancer Center

Professor and Chairman

Biography

Marc E. Lippman, M.D. was named the Kathleen and Stanley Glaser Professor of Medicine at the University of Miami Leonard M. Miller School of Medicine, and was named Chairman of the Department of Medicine in May 2007. Previously Dr. Lippman was the John G. Searle Professor and Chair of Internal Medicine at the University of Michigan, Ann Arbor, Michigan. From 1988 through 1999 Dr. Lippman was Professor of Medicine and Pharmacology, and Chair, Department of Oncology at Georgetown University in Washington, D.C., and served as Director of the Lombardi Cancer Center at Georgetown University Medical Center. From 1978 through 1990 he was Clinical Professor of Medicine and Pharmacology, Uniformed Services, University of the Health Sciences. Dr. Lippman served as Head of the Medical Breast Cancer Section, Medicine Branch, at the National Institute of Health. He was a Senior Investigator at the National Cancer Institute of the National Institute of Health. Dr. Lippman completed a Fellowship in Endocrinology at Yale Medical School in New Haven, CT from 1973-1974. In addition, he was Clinical Associate at the National Cancer Institute from 1970-1971 and Clinical Associate at the Laboratory of Biochemistry of the National Cancer Institute of the National Institute of Health. From 1970 to 1988 he served as an Officer and Medical Director of the United States Public Health Service. Dr. Lippman completed his residency on the Osler Medical Service, John Hopkins Hospital, in Baltimore, Maryland from 1968-1970.

A native of New York, Dr. Lippman received his Bachelor's Degree from Cornell University, Magna Cum Laude, and medical school degree at Yale Medical School in New Haven, CT where he was elected to AOA.

Dr. Lippman is widely known for his research in breast cancer. Throughout his illustrious career he has received numerous awards including Mallinckrodt Award of the Clinical Radioassay Society in 1978; the Commendation Medal USPHS in 1982; Meritorius Service Medal, USPHS in 1987; Clinical Investigator Award, American Federation for Clinical Research in 1985; D.R. Edwards Lecture and Medal, Tenovus Institute, Wales 1985; Plenary Lecturer, British Association of Cancer Research in 1987; Gosse Lecture, Dalhuosie University, Halifax Nova Scotia in 1987; the American Cancer Society.